umbilical cord blood transplantation in patients with hematologic malignancies using a myeloablative preparative regimen

Conditions: Hematologic Malignancies; Disorder Related to Transplantation; Hematopoietic Malignancy

Summary: in this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (hct), who do not have a suitable human leukocyte antigen (hla)-matched related/sibling donor (msd), matched unrelated donor (murd) or killer-immunoglobulin receptors (kir) ligand mismatched haploidentical donor identified, will receive an umbilical cord blood transplantation (ucbt) using a myeloablative preparative regimen. the preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation (tbi) (10.0 gy), and cyclophosphamide (120mg/kg) with mesna. fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, tbi will be given twice a day at 150 cgy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2. post-transplantation immunosuppression with cyclosporine and mmf will begin on day -3. cord blood infusion will occur on day 0 and g-csf will start on day +1.

the primary objectives is to estimate the event-free survival (efs) at one-year post-transplant for research participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (hct) using single unit umbilical cord blood (ucb). secondary objectives are: * describe the clinical outcome of patients undergoing a double unit ucbt. * estimate the incidence and severity of acute and chronic graft versus host disease (gvhd) of patients enrolled in the research arm. * estimate the incidence and time to neutrophil and platelet engraftment among patients enrolled in the research arm. * estimate the incidence of transplant related mortality (trm) and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research exploratory objectives are: * assess the relationship between pre-transplant minimal residual disease (mrd) with transplant outcomes. * record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, t cell receptor excision circle (trec) and spectratyping. immunophenotyping and functional assays of t, b and nk cells and lymphocytes will also be evaluated. * evaluate the determinants of engraftment.

Eligibility criteria:
inclusion criteria: * age less than or equal to 21 years old. * has a partially hla-matched single or double ucb product * high-risk hematologic malignancy. * high risk all in cr1, all in high risk cr2, all in cr3 or subsequent. * aml in high risk cr1, aml in cr2 or subsequent * aml in first relapse with \< 25% blasts in bm * therapy related aml, with prior malignancy in cr \> 12mo * mds, primary or secondary * nk cell, biphenotypic, or undifferentiated leukemia in cr1 or subsequent. * cml in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor. * hodgkin lymphoma in cr2 or subsequent after failure of prior autologous hct, or unable to mobilize stem cells for autologous hct. * non-hodgkin lymphoma in cr2 or subsequent after failure of prior autologous hct, or unable to mobilize stem cells for autologous hct. * jmml * all patients with evidence of cns leukemia must be treated and be in cns cr to be eligible for study. patient must fulfill pre-transplant evaluation: * cardiac shortening fraction ≥ 26%. * creatinine clearance ≥ 70 ml/min/1.73m2. * forced vital capacity (fvc) ≥ 50% of predicted value or pulse oximetry ≥ 92% on room air. * karnofsky (≥ 16 years) or lansky (\<16 years) performance score ≥ 70 * bilirubin ≤ 2.5 mg/dl. * alanine aminotransferase (alt) ≤ 5 times the upper limit of normal for age. * aspartate aminotransferase (ast) ≤ 5 times the upper limit of normal for age. exclusion criteria: * patient has a suitable msd, volunteer murd, or kir mismatched haploidentical donor available in the necessary time for stem cell donation. * patient has any other active malignancy other than the one for which hct is indicated. * patient had a prior allogeneic hct * patient had an autologous hct within the previous 12 months. * patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment. * patient is lactating * patient has down syndrome * patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the pi.

Keywords: hematologic malignancies umbilical cord blood transplantation hematopoietic cell transplantation